Lab Notes: The Education of a Stem Cell

Cancer stem cells play a key role in metastasis, but they need some help to form distant colonies, researchers led by Joerg Huelsken, PhD, of the Ecole Polytechnique Fédérale de Lausanne in Lausanne, Switzerland, reported in Nature.

In a series of experiments using a mouse model of breast cancer, the researchers showed that – without the stem cells – tumors do not establish new niche colonies in the lung, establishing their necessity for metastasis. But the stem cells have to prepare the ground first – stimulating production of a protein called periostin. When the researchers blocked periostin, metastasis failed.

The findings demonstrate that the "education" of stromal cells in the distant niche is an important part of metastatic colonization, the researchers reported, and preventing that step may be a novel therapeutic strategy.

-- M.S.

Couch Potatoes' Sugar Problem

Inactivity may lead to insulin resistance due to restricted capillary blood flow, researchers determined in a primate study.

Lean monkeys that didn't get much exercise showed greater insulin resistance as well as a blunted skeletal blood flow response both after glucose challenge and after exercise, which appeared to be because of poor flow through capillaries, the group reported at the 2011 European Association of Echocardiography meeting.

"Physical inactivity clearly correlates with microvascular dysfunction, which, in turn, can lead to insulin resistance," Scott Chadderdon, MD, of the Oregon Health and Science University in Portland said at the meeting. In a prior study, rats that went on an exercise program improved on both measures.

Together these results may explain why adding exercise is better than metformin alone at preventing diabetes, Chadderdon noted.

Although sleep problems have been associated with depression, it was thought that the mood disturbance begot the restless nights. To find out if the opposite might be true, Peter Meerlo, PhD, of the University of Groningen in the Netherlands, and colleagues deprived laboratory rats of sleep for days or weeks.

They found that sleep deprivation every night for a week induced altered regulation of the hypothalamic-pituitary-adrenal axis, an area of the brain involved in stress, mood, and emotion. A full month of restricted sleep caused shrinkage of the hippocampus, which is associated with memory and cognition.

In addition, the sleepy rats showed a reduced sensitivity of the serotonergic system, which regulates mood and emotion. "Many of these changes that we find look very much like depression," Meerlo said on a conference call with reporters.

The findings were reported at the American College of Neuropsychopharmacology meeting in Waikoloa, Hawaii.

MRI is typically used in stem cell studies, but CT is faster and and more widely dispersed among hospitals. It also is not limited by metallic implants such as pacemakers and defibrillators, noted Karl H. Schuleri, MD, from Johns Hopkins School of Medicine, and colleagues.

Compared with animals given placebo whose infarct size increased, those given mesenchymal stem cells had significantly reduced infarct size. The treatment group also had significantly increased ejection fractions compared with the placebo group, whose EFs decreased. The correlation of CT's assessment of LV volume, LV function, and infarct size with MRI was "favorable."

But for CT to become routine in clinical trials, low-dose protocols would have to become standardized, researchers reported in the December issue of the Journal of the American College of Cardiology: Cardiovascular Imaging.

-- C.K.

Prickly Pathway May Lead to New Cancer Therapy

Development of a new class of small-molecule inhibitor for cancer has run head-on into a porcupine.

A potent candidate inhibitor of the Wnt pathway zeroed in on a protein known as porcupine. The protein controls a key step in the secretion of Wnt ligands, which have been linked to mammary carcinogenesis in a mouse model of breast cancer.

Inhibition of porcupine blocked a variety of Wnt-dependent activities. In one preclinical evaluation, the porcupine inhibitor, known as NVP-LGK974, "robustly suppressed Wnt pathway signaling in vivo, resulting in tumor regression in a murine breast cancer model driven by MMTV-Wnt1," investigators at the Genomics Institute of the Novartis Research Foundation in San Diego reported at the San Antonio Breast Cancer Symposium.

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